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We present observations of four rapidly rising (trise ≈ 10 days) transients with peak luminosities between those of supernovae (SNe) and superluminous SNe (Mpeak ap; -20) - one discovered and followed by the Palomar Transient Factory (PTF) and three by the Supernova Legacy Survey. The light curves resemble those of SN 2011kl, recently shown to be associated with an ultra-long-duration gamma-ray burst (GRB), though no GRB was seen to accompany our SNe. The rapid rise to a luminous peak places these events in a unique part of SN phase space, challenging standard SN emission mechanisms. Spectra of the PTF event formally classify it as an SN II due to broad Hα emission, but an unusual absorption feature, which can be interpreted as either high velocity Hα (though deeper than in previously known cases) or Si ii (as seen in SNe Ia), is also observed. We find that existing models of white dwarf detonations, CSM interaction, shock breakout in a wind (or steeper CSM), and magnetar spin down cannot readily explain the observations. We consider the possibility that a "Type 1.5 SN" scenario could be the origin of our events. More detailed models for these kinds of transients and more constraining observations of future such events should help to better determine their nature.

The intermediate Palomar Transient Factory (iPTF) detection of the most recent outburst of the recurrent nova (RN) system RX J0045.4+4154 in the Andromeda galaxy has enabled the unprecedented study of a massive (M > 1.3 M) accreting white dwarf (WD). We detected this nova as part of the near-daily iPTF monitoring of M31 to a depth of R 21 mag and triggered optical photometry, spectroscopy and soft X-ray monitoring of the outburst. Peaking at an absolute magnitude of MR= -6.6 mag, and with a decay time of 1 mag per day, it is a faint and very fast nova. It shows optical emission lines of He/N and expansion velocities of 1900-2600 km s-1 1-4 days after the optical peak. The Swift monitoring of the X-ray evolution revealed a supersoft source (SSS) with kT eff 90-110 eV that appeared within 5 days after the optical peak, and lasted only 12 days. Most remarkably, this is not the first event from this system, rather it is an RN with a time between outbursts of approximately 1 yr, the shortest known. Recurrent X-ray emission from this binary was detected by ROSAT in 1992 and 1993, and the source was well characterized as a M > 1.3 M WD SSS. Based on the observed recurrence time between different outbursts, the duration and effective temperature of the SS phase, MESA models of accreting WDs allow us to constrain the accretion rate to and WD mass >1.30 M. If the WD keeps 30% of the accreted material, it will take less than a Myr to reach core densities high enough for carbon ignition (if made of C/O) or electron capture (if made of O/Ne) to end the binary evolution. © 2014. The American Astronomical Society. All rights reserved..

Conformational flexibility is one of the main disadvantages of peptide-based compounds. We focus on their molecular 'chameleonicity' related to forming pseudo-cyclic motifs via modulation of weak intramolecular interactions. It is an appealing strategy for controlling equilibrium between the polar open and the nonpolar closed conformations. Within this context, we report here the crystal structure of the ( R )-(2- tert -butoxycarbonyl)amino-1-oxo-3-phenyl)propyl)-1-cyclopentene ( 1 ), synthesis of which in high yield was achieved by a facile multi-step protocol. Our Cambridge Structural Database (CSD) overview for the peptide-based crystals revealed the exclusivity of this compound from the viewpoint of the unusual pseudo-bicyclic system via C-H … O and C-O … π interactions, in which cyclopentene shields the amide bond. Notably, cyclopentene as a bioisostere of proline is an appealing scaffold in medicinal chemistry. An extensive combined experimental and computational study provided more profound insight into the supramolecular landscape of 1 with respect to similar derivatives deposited in the CSD, including the tendency of cyclopentene for the generation of pseudo-cyclic motifs through weak H-bonding and π-based intramolecular interactions. These weak interactions have been examined by either the quantum theory of 'atoms-in-molecules' (QTAIM) or complex Hirshfeld surface methodology, including enrichment ratios, molecular electrostatic potential surfaces and energy frameworks. In all analysed crystals, all types of H-bonded motifs involving cyclopentene are formed at all levels of supramolecular architecture. A library of cyclopentene-based H-bonding synthons is provided. A molecular docking study depicted vital interactions of cyclopentene with key amino acid residues inside the active sites of two prominent protein kinases, uncovering the therapeutic potential of 1 against breast cancer. To a large extent, dispersion forces have significance in stabilizing the supramolecular structure of both ligand and bio-complex ligand-protein. Finally, the satisfactory in silico bio-pharmacokinetic profile of 1 related to drug-likeness and blood-brain barrier permeation was also revealed., Competing Interests: We declare we have no competing interests., (© 2024 The Author(s).)

Short peptides have been coming around as a strong weapon in the fight against cancer on all fronts-in immuno-, chemo-, and radiotherapy, and also in combinatorial approaches. Moreover, short peptides have relevance in cancer imaging or 3D culture. Thanks to the natural 'smart' nature of short peptides, their unique structural features, as well as recent progress in biotechnological and bioinformatics development, short peptides are playing an enormous role in evolving cutting-edge strategies. Self-assembling short peptides may create excellent structures to stimulate cytotoxic immune responses, which is essential for cancer immunotherapy. Short peptides can help establish versatile strategies with high biosafety and effectiveness. Supramolecular short peptide-based cancer vaccines entered clinical trials. Peptide assemblies can be platforms for the delivery of antigens, adjuvants, immune cells, and/or drugs. Short peptides have been unappreciated, especially in the vaccine aspect. Meanwhile, they still hide the undiscovered unlimited potential. Here, we provide a timely update on this highly active and fast-evolving field.

The unique physicochemical properties and fascinating bioisosterism of tetrazole scaffolds have received significant attention in medicinal chemistry. We report recent efforts using tetrazoles in drug design strategies in this context. Despite the increasing prevalence of tetrazoles in FDA-approved drugs for various conditions such as cancer, bacterial viral and fungal infections, asthma, hypertension, Alzheimer's disease, malaria, and tuberculosis, our understanding of their structure-activity relationships, multifunctional mechanisms, binding modes, and biochemical properties remains limited. We explore the potential of tetrazole bioisosteres in optimising lead molecules for innovative therapies, discussing applications, trends, advantages, limitations, and challenges. Additionally, we assess future research directions to drive further progress in this field., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The anti-inflammatory, antiviral, and anti-cancer properties, as well as the mechanism of action of cyclo-[Pro-Pro- β 3 -HoPhe-Phe-] tetrapeptide (denoted as 4B8M), were recently described. The aim of this work was to synthesize and evaluate the immunosuppressive actions of the stereochemical variants of 4B8M by sequential substitution of L -amino acids by D -amino acids (a series of peptides denoted as P01-P07) using parent 4B8M as a reference compound. In addition, diverse available bioinformatics tools using machine learning and artificial intelligence were tested to find the bio-pharmacokinetic and polypharmacological attributes of analyzed stereomers. All peptides were non-toxic to human peripheral blood mononuclear cells (PBMCs) and only cyclo-[ D -Pro-Pro- β 3 -HoPhe-Phe-] peptide (P03) was capable of inhibiting mitogen-induced PBMC proliferation. The peptides inhibited the lipopolysaccharide (LPS)-induced production of tumor necrosis factor-alpha (TNF-α) to various degrees, with P04 (cyclo-[Pro-Pro- D - β 3 -HoPhe-Phe-]) and P03 being the most potent. For further in vivo studies, P03 was selected because it had the combined properties of inhibiting cell proliferation and TNF-α production. P03 demonstrated a comparable ability to 4B8M in the inhibition of auricle edema and lymph node cell number and in the normalization of a distorted blood cell composition in contact sensitivity to the oxazolone mouse model. In the mouse model of carrageenan-induced inflammation of the air pouch, P03 exhibited a similar inhibition of the cell number in the air pouches as 4B8M, but its inhibitory effects on the percentage of neutrophils and eosinophils in the air pouches and blood, as well as on mastocyte degranulation in the air pouches, were stronger in comparison to 4B8M. Lastly, in a mouse model of dextran sulfate-induced colitis, similar effects to 4B8M regarding thymocyte number restoration and normalization of the blood cell pictures by P03 were observed. In summary, depending on either experimental findings or in silico predictions, P03 demonstrated comparable, or even better, anti-inflammatory and bio-pharmacokinetic properties to 4B8M and may be considered as a potential therapeutic. The possibility of P00 and P03 identification by circular dichroism measurements was tested by quantum-chemical calculations.

Clathrate hydrates are among the most intensively studied H-bond inclusion compounds. Despite the broad definition for this class of compounds, their meaning commonly refers to closed polyhedral nanocages that encapsulate small guest molecules. On the other hand, larger solutes enforce another type of encapsulation because of the solute size effect. Herein, we report a series of structures containing various molecules encapsulated by intercalated water layers constructed of polycyclic moieties of L4(4)8(8) topology. We parametrized the corrugation of individual layers and characterized interactions governing their formation. We suggested that these could be categorized as two-dimensional clathrates based on the character of intra-layer interactions and the effects observed between entrapped molecules and water-based intercalators., (© 2024 Wiley-VCH GmbH.)

Four alkaline earth metal complexes of ketoprofen (Hket) and indomethacin (Hind) were synthesized and characterized: [Ca(ket) 2 (H 2 O) 2 ] n (1), [Mg(ket) 2 (H 2 O) 2 ] (2), [Ca(ind) 2 (EtOH) 2 ] n (3), and [Mg(ind) 2 (EtOH) 2 ] (4). All compounds were studied by elemental analysis (EA), flame atomic absorption spectrometry (FAAS), Fourier transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA). Crystal structures of 1 and 3 were determined by single crystal X-ray diffraction technique T=100 K. The structure of 1 is dominated by a one-dimensional coordination polymer, while 3 is formed by a two-dimensional layer stabilized by the calcium zig-zag chains and π⋅⋅⋅π stacking interactions. Crystal packing arrangements were characterized by fingerprint plots (FPs) that were derived from the Hirshfeld surfaces (HSs). The antioxidant and antimicrobial activities of complexes were evaluated against Gram-positive and Gram-negative bacteria as well as yeasts., (© 2024 Wiley-VCH GmbH.)

With the pronounced increase in nanotechnology, it is likely that biological systems will be exposed to excess nanoparticles (NPs). Cerium oxide nanoparticles (CeO 2 NPs) are among the most abundantly produced nanomaterials in the world. Their widespread use raises fundamental questions related to the accumulation in the environment and further interactions with living organisms, especially plants. NPs present in either soil or soilless environments are absorbed by the plant root systems and further transported to the aboveground parts. After entering the cytoplasm, NPs interact with chloroplast, nucleus, and other structures responsible for metabolic processes at the cellular level. In recent years, several studies have shown the impact of nanoceria on plant growth and metabolic processes. Research performed on different plants has shown a dual role for CeO 2 NPs. The observed effects can be positive or negative and strongly depend on the plant species, characterization, and concentrations of NPs. This review describes the impact of root-applied CeO 2 NPs on plant growth, photosynthesis, metal homeostasis, and parameters of induced oxidative stress., Competing Interests: The authors declare no conflicts of interest.

This work is aimed at relationships which govern zinc and copper uptake by four popular medicinal herbs: basil ( Ocimum basilicum L.), borage (Borago officinalis L.), common nettle ( Urtica dioica L.) and peppermint ( Mentha piperita L.). They are often grown in soils with significant copper or zinc levels. Herbs were cultivated by a pot method in controlled conditions. Manganese, iron, copper and zinc concentrations were determined by High-Resolution Continuum Source Flame Atomic Absorption Spectrometry. The efficiency of photosynthesis was estimated by measuring the chlorophyll content, water use efficiency, net photosynthesis, intercellular CO 2 , stomatal conductance, and transpiration rate. Phenolic compounds were determined by the Folin-Ciocalteu method. Analysis of variance showed that herbs grown in soil treated with copper exhibited a lower iron content in roots, while manganese behaved in the opposite way. The only exception was borage, where a decrease in the manganese content in roots was observed. Both copper and zinc supplementations increased the total content of phenolics, while the highest increases were observed for common nettle and basil. Peppermint and borage responded less to supplementation. In the majority of samples, zinc and copper did not significantly affect the photosynthesis. Herbal extracts from common nettle and basil had unique antioxidant properties and may be good free radical scavengers.

The surface water pollution can cause serious ecological disasters. An example is large-scale fish deaths due to excessive salinity, which is global problem. In order to prevent such situations, it is necessary to carry out regular monitoring of both main rivers and their tributaries. The current monitoring system is neither adapted to the variability associated with the diversified use of catchments nor to changing climatic conditions. The Bzura River is one of the most anthropogenically transformed Polish rivers. So far, no comprehensive assessment of the chemical status of its catchment has been carried out. The presented research is a continuation of the study of the spatio-temporal variability of the Bzura chemistry. It covered 19 tributaries within the boundaries of the Łódź Voivodeship. Samples were collected once a month for one hydrological year. In total, 228 samples were obtained, in which 21 parameters were measured. Spatio-temporal variability of water quality on the basis of coefficients of variation (CVs) and water quality indices (WQIs) was evaluated. Principal component analysis (PCA) and cluster analysis (CA) were also performed. In addition, the datasets were visualized using geochemical maps. Combined monitoring with geospatial analysis brings benefits in terms of efficient control and management of water resources. The tributaries were divided according to the degree of their pollution. It was found that the electrical conductivity and concentrations of dissolved oxygen, nitrates, calcium and magnesium differentiated the tributaries in terms of pollution the most. The strong salinity from agricultural and geogenic sources was found. The WQIs were higher for the tributaries than for the Bzura. It suggests that the Bzura may be polluted by the tributaries under "favorable" climatic and hydrological conditions. Therefore, smaller watercourses should be included in monitoring and become more important in terms of an effective solution to global problem of surface water pollution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Wide availability of anthropogenic TiO 2 nanoparticles facilitates their penetration into environment and prompts interactions with plants. They alter plants growth and change their nutritional status. In particular, metabolic processes are affected. In this work the effect of nanometric TiO 2 on photosynthesis efficiency in green pea (Pisum sativum L.) was studied. Hydroponic cultivations with three Ti levels (10; 50 and 100 mg L -1 ) were applied. At all concentrations nanoparticles penetrated into plant tissues and were detected by the single particle ICP-MS/MS method. Nanoparticles altered the CO 2 assimilation rate and gas exchange parameters (i.e. transpiration, stomatal conductance, sub-stomatal CO 2 concentration). The most pronounced effects were observed for Ti 50 mg L -1 cultivation where photosynthesis efficiency, transpiration and stomatal conductance were increased by 14.69%, 4.58% and 8.92%, respectively. They were further confirmed by high maximum ribulose 1,5-bisphosphate carboxylation rate (27.40% increase), maximum electron transport rate (21.51% increase) and the lowest CO 2 compensation point (45.19% decrease). Furthermore, concentrations of Cu, Mn, Zn, Fe, Mg, Ca, K and P were examined with the most pronounced changes observed for elements directly involved in photosynthesis (Cu, Zn, Mn, and Fe). The Cu concentrations in roots, stems and leaves for Ti 50 mg L -1 cultivation were below the control by 33.15%, 38.28% and 10.76%, respectively. The Zn content in analogous treatment and organs decreased by 30.24%, 26.69% and 13.35%. The Mn and Fe levels in leaves were increased by 72.22% and 50.32%, respectively. Our results indicated that plant defence mechanisms which restrain the water uptake have been overcome in pea by photocatalytic activity of nanoparticulate TiO 2 which stimulated photosynthesis. On the contrary to the substantial stomatal conductance, the transpiration has been reduced because exceptional part of water flow was already consumed in chloroplasts and could not have been freed to the atmosphere., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The aim of this study was to assess influence of cadmium and zinc treatments on antioxidant activity combined with the photosynthesis efficiency in a popular herb lemon balm ( Melissa officinalis L.). Plants were grown under greenhouse conditions by the pot method. The Mn, Cu, Cd, and Zn contents in soil and plants were measured by HR-CS FAAS. The activity of net photosynthesis, stomatal conductance, transpiration rate, intercellular CO 2 , and index of chlorophyll in leaves were determined for all investigated species. Reduction of the net photosynthesis was observed for cultivations subjected to either Zn or Cd treatments. Phenolic contents were determined by the chemical Folin-Ciocalteu method, while enhanced voltammetric analysis was applied to assess the antioxidant properties of plant extracts. Both of these approaches yielded similar results. Herbal extracts had exceptional antioxidant capacities and were good scavengers of free radicals and reactive oxygen species. Structural similarity of cadmium and zinc facilitated their mutual structural exchange and prompted substantial expansion of phenolics under the mixed Zn and Cd treatments.

This study was a continuation of our investigation of the spatio-temporal variability of the Bzura River's water chemistry. Our research is of particular importance in the context of the recent ecological disaster on the Oder River and concerns the international problem of surface water contamination. The study area was a 120 km section of the Bzura River. We tested more measurement points and with a higher sampling frequency than those used in the national monitoring of river water quality. During two hydrological years, 360 water samples were collected. The selected parameters: electrical conductivity, temperature, dissolved oxygen, dissolved organic carbon, nitrates, phosphates, bicarbonates, chlorides, sodium, potassium, calcium, and magnesium were determined. Numerous results exceeded the Polish threshold limits. Spatio-temporal variability and water quality were assessed using principal component analysis (PCA), cluster analysis (CA), and water quality index (WQI) approaches. Many point sources of pollution related to urbanization, agriculture, and industry were detected. Moreover, due to the changing climatic conditions, a significant difference between temporal variability in both years was observed. Our results indicated that it is necessary to increase the number of measurement stations for surface water monitoring; it will allow for a faster detection of the threat.

Herbs used in medicine should be grown under controlled and standardized conditions. Agricultural practices often induce changes to soil pH, which may affect migration of heavy metals in the environment, their accumulation in plant tissues and the concentration of medicinal ingredients. The aim of this work was to assess the influence of various soil pH on the biological parameters and uptake of manganese, copper and zinc by basil, dandelion and lemon balm. The soil analysis covered pH, organic matter content, bioavailable and total forms of investigated metals in soil. In plants cultivated in soil at pH covering the range 4.7-8.5 the concentrations of Mn, Cu and Zn were analyzed. Their mobility and availability were assessed by bioaccumulation factors, translocation factors and transfer coefficients. The seed germination and subsequent herbs growth were strongly dependent on soil pH for all investigated plant species. Photosynthetic efficiency at different pHs was positively correlated with uptake of Cu and Mn while Zn behaved in a more random way.

Short peptides have great potential as safe and effective anticancer drug leads. Herein, the influence of short cyclic peptides containing the Pro-Pro-Phe-Phe sequence on patient-derived melanoma cells was investigated. Cyclic peptides such as cyclo(Leu-Ile-Ile-Leu-Val-Pro-Pro-Phe-Phe-), called CLA, and cyclo(Pro-homoPro-β 3 homoPhe-Phe-), called P11, exert the cytotoxic and the cytostatic effects in melanoma cells, respectively. CLA was the most active peptide as it reduced the viability of melanoma cells to 50% of control at about 10 µM, whereas P11 at about 40 µM after 48 h incubation. Interestingly, a linear derivative of P11 did not induce any effect in melanoma cells confirming previous studies showing that cyclic peptides exert better biological activity compared to their linear counterparts. According to in silico predictions, cyclic tetrapeptides show a better pharmacokinetic and toxic profile to humans than CLA. Notably, the spatial structure of those peptides containing synthetic amino acids has not been explored yet. In the Cambridge Structural Database, there is only one such cyclic tetrapeptide, cyclo((R)-β 2 homoPhe-D-Pro-Lys-Phe-), while in the Protein Data Bank-none. Therefore, we report the first crystal structure of cyclo(Pro-Pro-β 3 homoPhe-Phe-), denoted as 4B8M, a close analog of P11, which is crucial for drug discovery. Comparative molecular and supramolecular analysis of both structures was performed. The DFT findings revealed that 4B8M is well interpreted in the water solution. The results of complex Hirshfeld surface investigations on the cooperativity of interatomic contacts in terms of electrostatic and energetic features are provided. In short, the enrichment ratio revealed O … H/H … O and C … H/H … C as privileged intercontacts in the crystals in relation to basic and large supramolecular H-bonding synthon patterns. Furthermore, the ability of self-assemble 4B8M leading to a nanotubular structure is also discussed.

Cerium oxide nanoparticles (CeO 2 NPs) and zinc oxide nanoparticles (ZnO NPs) are emerging pollutants that are likely to occur in the contemporary environment. So far, their combined effects on terrestrial plants have not been thoroughly investigated. Obviously, this subject is a challenge for modern ecotoxicology. In this study, Pisum sativum L. plants were exposed to either CeO 2 NPs or ZnO NPs alone, or mixtures of these nano-oxides (at two concentrations: 100 and 200 mg/L). The plants were cultivated in hydroponic system for twelve days. The combined effect of NPs was proved by 1D ANOVA augmented by Tukey's post hoc test at p = 0.95. It affected all major plant growth and photosynthesis parameters. Additionally, HR-CS AAS and ICP-OES were used to determine concentrations of Cu, Mn, Fe, Mg, Ca, K, Zn, and Ce in roots and shoots. Treatment of the pea plants with the NPs, either alone or in combination affected the homeostasis of these metals in the plants. CeO 2 NPs stimulated the photosynthesis rate, while ZnO NPs prompted stomatal and biochemical limitations. In the mixed ZnO and CeO 2 treatments, the latter effects were decreased by CeO 2 NPs. These results indicate that free radicals scavenging properties of CeO 2 NPs mitigate the toxicity symptoms induced in the plants by ZnO NPs.

Cyclic dipeptides, also know as diketopiperazines (DKP), the simplest cyclic forms of peptides widespread in nature, are unsurpassed in their structural and bio-functional diversity. DKPs, especially those containing proline, due to their unique features such as, inter alia, extra-rigid conformation, high resistance to enzyme degradation, increased cell permeability, and expandable ability to bind a diverse of targets with better affinity, have emerged in the last years as biologically pre-validated platforms for the drug discovery. Recent advances have revealed their enormous potential in the development of next-generation theranostics, smart delivery systems, and biomaterials. Here, we present an updated review on the biological and structural profile of these appealing biomolecules, with a particular emphasis on those with anticancer properties, since cancers are the main cause of death all over the world. Additionally, we provide a consideration on supramolecular structuring and synthons, based on the proline-based DKP privileged scaffold, for inspiration in the design of compound libraries in search of ideal ligands, innovative self-assembled nanomaterials, and bio-functional architectures.

Dandelion (Taraxacum officinale) yields active substances frequently used in herbal medicinal preparations. Its plantations are exposed to fungal plagues which pose a threat to herbal crops. The aim of this study was to evaluate the long time effects of a fungicide thiuram on dandelion growth and photosynthesis. Additionally, the manganese, iron, copper, zinc, cadmium, and lead uptake and transport were also investigated. Plants were cultivated under greenhouse conditions by the pot method in a universal flowering soil. The elements content in soil and plants were determined by the HR-CS FAAS spectrometer. Thiuram concentrations were established by the HPLC. Those analyses showed that almost 80% of thiuram decomposed within two weeks of its application. The photosynthesis indicators suggested, that plants were in good conditions and the fungicide supplementation facilitated plant growth. The latter could be prompted by thiuram acting as a sulfur rich chemical micro fertilizer. The hypothesis, that thiuram significantly affects heavy metals interactions in dandelion was proved by the one-way analysis of variance. Notable, metals uptake did not completely recover after fungicide decomposition for all investigated elements except iron We suggest to define this chemically induced, time-dependent heavy metals migrations in the soil-plant system as hysteresis of heavy metals uptake., (© 2021. The Author(s).)

Targeting the polyamine biosynthetic pathway by inhibiting ornithine decarboxylase (ODC) is a powerful approach in the fight against diverse viruses, including SARS-CoV-2. Difluoromethylornithine (DFMO, eflornithine) is the best-known inhibitor of ODC and a broad-spectrum, unique therapeutical agent. Nevertheless, its pharmacokinetic profile is not perfect, especially when large doses are required in antiviral treatment. This article presents a holistic study focusing on the molecular and supramolecular structure of DFMO and the design of its analogues toward the development of safer and more effective formulations. In this context, we provide the first deep insight into the supramolecular system of DFMO supplemented by a comprehensive, qualitative and quantitative survey of non-covalent interactions via Hirshfeld surface, molecular electrostatic potential, enrichment ratio and energy frameworks analysis visualizing 3-D topology of interactions in order to understand the differences in the cooperativity of interactions involved in the formation of either basic or large synthons (Long-range Synthon Aufbau Modules, LSAM) at the subsequent levels of well-organized supramolecular self-assembly, in comparison with the ornithine structure. In the light of the drug discovery, supramolecular studies of amino acids, essential constituents of proteins, are of prime importance. In brief, the same amino-carboxy synthons are observed in the bio-system containing DFMO. DFT calculations revealed that the biological environment changes the molecular structure of DFMO only slightly. The ADMET profile of structural modifications of DFMO and optimization of its analogue as a new promising drug via molecular docking are discussed in detail., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bojarska, New, Borowiecki, Remko, Breza, Madura, Fruziński, Pietrzak and Wolf.)

Objectives: We sought to study the impact of COVID-19 pandemic on the presentation delay, severity, patterns of care, and reasons for delay among patients with ST-elevation myocardial infarction (STEMI) in a non-hot-spot region., Background: COVID-19 pandemic has significantly reduced the activations for STEMI in epicenters like Spain., Methods: From January 1, 2020, to April 15, 2020, 143 STEMIs were identified across our integrated 18-hospital system. Pre- and post-COVID-19 cohorts were based on March 23rd, 2020, whenstay-at-home orders were initiated in Ohio. We used presenting heart rate, blood pressure, troponin, new Q-wave, and left ventricle ejection fraction (LVEF) to assess severity. Duration of intensive care unit stay, total length of stay, door-to-balloon (D2B) time, and radial versus femoral access were used to assess patterns of care., Results: Post-COVID-19 presentation was associated with a lower admission LVEF (45 vs. 50%, p = .015), new Q-wave, and higher initial troponin; however, these did not reach statistical significance. Among post-COVID-19 patients, those with >12-hr delay in presentation 31(%) had a longer average D2B time (88 vs. 53 min, p = .033) and higher peak troponin (58 vs. 8.5 ng/ml, p = .03). Of these, 27% avoided the hospital due to fear of COVID-19, 18% believed symptoms were COVID-19 related, and 9% did not want to burden the hospital during the pandemic., Conclusions: COVID-19 has remarkably affected STEMI presentation and care. Patients' fear and confusion about symptoms are integral parts of this emerging public health crisis., (© 2020 Wiley Periodicals LLC.)

Peptides are fragments of proteins that carry out biological functions. They act as signaling entities via all domains of life and interfere with protein-protein interactions, which are indispensable in bio-processes. Short peptides include fundamental molecular information for a prelude to the symphony of life. They have aroused considerable interest due to their unique features and great promise in innovative bio-therapies. This work focusing on the current state-of-the-art short peptide-based therapeutical developments is the first global review written by researchers from all continents, as a celebration of 100 years of peptide therapeutics since the commencement of insulin therapy in the 1920s. Peptide "drugs" initially played only the role of hormone analogs to balance disorders. Nowadays, they achieve numerous biomedical tasks, can cross membranes, or reach intracellular targets. The role of peptides in bio-processes can hardly be mimicked by other chemical substances. The article is divided into independent sections, which are related to either the progress in short peptide-based theranostics or the problems posing challenge to bio-medicine. In particular, the SWOT analysis of short peptides, their relevance in therapies of diverse diseases, improvements in (bio)synthesis platforms, advanced nano-supramolecular technologies, aptamers, altered peptide ligands and in silico methodologies to overcome peptide limitations, modern smart bio-functional materials, vaccines, and drug/gene-targeted delivery systems are discussed.

Cerium dioxide nanoparticles are pollutants of emerging concern. They are rarely immobilized in the environment. This study extends our work on Pisum sativum L. as a model plant, cultivated worldwide, and is well suited for investigating additive interactions induced by nanoceria. Hydroponic cultivation, which prompts accurate plant growth control and three levels of CeO 2 supplementation, were applied, namely, 100, 200, and 500 mg (Ce)/L. Phytotoxicity was estimated by fresh weights and photosynthesis parameters. Additionally, Ce, Cu, Zn, Mn, Fe, Ca, and Mg contents were analyzed by high-resolution continuum source atomic absorption and inductively coupled plasma optical emission techniques. Analysis of variance has proved that CeO 2 nanoparticles affected metals uptake. In the roots, it decreased for Cu, Zn, Mn, Fe, and Mg, while a reversed process was observed for Ca. The latter is absorbed more intensively, but translocation to above-ground parts is hampered. At the same time, nanoparticulate CeO 2 reduced Cu, Zn, Mn, Fe, and Ca accumulation in pea shoots. The lowest Ce concentration boosted the photosynthesis rate, while the remaining treatments did not induce significant changes. Plant growth stimulation was observed only for the 100 mg/L. To our knowledge, this is the first study that demonstrates the effect of nanoceria on photosynthesis-related parameters in peas.

Proline is a unique, endogenous amino acid, prevalent in proteins and essential for living organisms. It is appreciated as a tecton for the rational design of new bio-active substances. Herein, we present a short overview of the subject. We analyzed 2366 proline-derived structures deposited in the Cambridge Structure Database, with emphasis on the angiotensin-converting enzyme inhibitors. The latter are the first-line antihypertensive and cardiological drugs. Their side effects prompt a search for improved pharmaceuticals. Characterization of tectons (molecular building blocks) and the resulting supramolecular synthons (patterns of intermolecular interactions) involving proline derivatives, as presented in this study, may be useful for in silico molecular docking and macromolecular modeling studies. The DFT, Hirshfeld surface and energy framework methods gave considerable insight into the nature of close inter-contacts and supramolecular topology. Substituents of proline entity are important for the formation and cooperation of synthons. Tectonic subunits contain proline moieties characterized by diverse ionization states: -N and -COOH(-COO - ), -N + and -COOH(-COO - ), -NH and -COOH(-COO - ), -NH + and -COOH(-COO - ), and -NH 2 + and -COOH(-COO - ). Furthermore, pharmacological profiles of ACE inhibitors and their impurities were determined via an in silico approach. The above data were used to develop comprehensive classification, which may be useful in further drug design studies.

The pollution of urban soils by metals is a global problem. Prolonged exposure of habitants who are in contact with metals retained in soil poses a health risk. This particularly applies to industrialized cities with developed transport networks. The aim of the study was to determine the content and spatial distribution of mobile metal fractions in soils of the city of Łódź and to identify their load and sources. Multivariate statistical analysis (principal component analysis (PCA), cluster analysis (CA)), combined with GIS, were used to make a comprehensive evaluation of the soil contamination. Hot-spots and differences between urban and suburban areas were also investigated. Metals were determined by atomic absorption spectrometry (AAS) after soil extraction with 1 mol L -1 HCl. In most sites, the metal content changes in the following order: Zn > Pb > Cu > Ni > Cd. About one-third of the samples are considerably (or very highly) contaminated, (contamination factor, CF > 3) with Cu, Pb, or Zn. In almost 40% of the samples, contaminated soils were found (pollution load index, PLI > 1). All metals have a strong influence on the first principal component (PC1), whereas second principal component (PC2) is related to pH. Polluted soils are located in the downtown, in the south and east part of the city. The distribution of contamination coincides with the urban layout, low emission sources and former industrial areas of Łódź.

Five complexes of Mn(II), Co(II), Ni(II), Cu(II) and Zn(II) with non-steroidal anti-inflammatory drug, flufenamic acid were synthesized: (1) [Mn 3 (fluf) 6 EtOH)(H 2 O)] · 3EtOH; (2) [Co(fluf) 2 (EtOH)(H 2 O)] · H 2 O; (3) [Ni(fluf) 2 (EtOH)(H 2 O)] · H 2 O; (4) [Cu(fluf) 2· H 2 O]; (5) [Zn(fluf) 2· H 2 O]. All complexes were characterized by elemental analysis (EA), flame atomic absorption spectrometry (FAAS), Fourier-transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA). The crystal structure of 1 was determined by the single crystal X-ray diffraction technique. It crystallizes in the triclinic space group P with three independent Mn(II) cations, six coordinated flufenamato ligands augmented with water and ethanol molecules in the inner coordination sphere. In this crystal, manganese atoms are multiplied by symmetry and form infinite, polymeric chains which extend along the [001] dimension. The Hirshfeld Surface analysis revealed changes in interaction assemblies around all metal centers. The antioxidant and antimicrobial activities were established for all complexes and free ligand for comparison. All compounds exhibit good or moderate bioactivity against Gram-positive bacteria and yeasts.

Widespread occurrence of ZnO nanoparticles in environment follows the growing number of applications either in technology or agriculture. The impact of five forms of nanoparticulate ZnO on copper, manganese and iron uptake by Pisum sativum L. cultivated in Hoagland solutions was investigated. Plants were collected after twelve days of zinc administration. Effect of bulk ZnO has also been studied. Initial zinc concentration was 100 mg L -1 . Nanoparticles were characterized by the Transmission Electron Microscopy, Dynamic Light Scattering and Zeta potential measurements. Metal contents were analyzed using the Atomic Absorption Spectrometry with flame atomization for samples digested in a microwave closed system. Analysis of variance indicated that zinc species at either molecular or nanoscale levels altered Cu, Mn and Fe uptake and their further transport in pea plants. In particular, significant reduction of Mn and Fe combined with the Cu increase was observed. Additive interactions originated by nanoparticles affect the heavy metals uptake and indicate pollutants migration pathways in plants. Unfortunately, regulations for the plant cultivation were formulated when anthropogenic nanoparticles were not in common use. They underestimate complexity of metals interactions in either plant or habitat. Our results indicate that these additive interactions cannot be neglected and deserve further investigations.

Three metal complexes of mefenamato ligand 1 were synthesized: [Co 2 (mef) 4 (EtOH) 2 (H 2 O) 4 ]: 2 ; [Co(mef) 2 (MeOH) 4 ]∙2MeOH: 3 ; and [Ni(mef) 2 (MeOH) 4 ]∙2MeOH: 4 . Their compositions and properties were investigated by elemental analysis (EA), flame atomic absorption spectrometry (FAAS), Fourier-transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA). Crystal structures were determined by the single crystal X-ray diffraction technique. Additionally, their antioxidant and antimicrobial activity were established, thus proving good/moderate bioactivity against Gram-positive bacteria and yeasts. In the crystal structure of 2 , an apical water molecule is shared between two adjacent cobalt(II) ions, resulting in the formation of a polymeric chain extending along the [100] direction. Meanwhile, structures 3 and 4 have strong intermolecular hydrogen bonds with diverse topologies that yield unique quasi-isostructural arrangements. The packing topology is reflected by the Hirshfeld surface analysis of intermolecular contacts.

Recently, fluorenylmethoxycarbonyl (Fmoc) amino acids (e.g. Fmoc-tyrosine or Fmoc-phenylalanine) have attracted growing interest in biomedical research and industry, with special emphasis directed towards the design and development of novel effective hydrogelators, biomaterials or therapeutics. With this in mind, a systematic knowledge of the structural and supramolecular features in recognition of those properties is essential. This work is the first comprehensive summary of noncovalent interactions combined with a library of supramolecular synthon patterns in all crystal structures of amino acids with the Fmoc moiety reported so far. Moreover, a new Fmoc-protected amino acid, namely, 2-{[(9H-fluoren-9-ylmethoxy)carbonyl](methyl)amino}-3-{4-[(2-hydroxypropan-2-yl)oxy]phenyl}propanoic acid or N-fluorenylmethoxycarbonyl-O-tert-butyl-N-methyltyrosine, Fmoc-N-Me-Tyr(t-Bu)-OH, C 29 H 31 NO 5 , was successfully synthesized and the structure of its unsolvated form was determined by single-crystal X-ray diffraction. The structural, conformational and energy landscape was investigated in detail by combined experimental and in silico approaches, and further compared to N-Fmoc-phenylalanine [Draper et al. (2015). CrystEngComm, 42, 8047-8057]. Geometries were optimized by the density functional theory (DFT) method either in vacuo or in solutio. The polarizable conductor calculation model was exploited for the evaluation of the hydration effect. Hirshfeld surface analysis revealed that H...H, C...H/H...C and O...H/H...O interactions constitute the major contributions to the total Hirshfeld surface area in all the investigated systems. The molecular electrostatic potentials mapped over the surfaces identified the electrostatic complementarities in the crystal packing. The prediction of weak hydrogen-bonded patterns via Full Interaction Maps was computed. Supramolecular motifs formed via C-H...O, C-H...π, (fluorenyl)C-H...Cl(I), C-Br...π(fluorenyl) and C-I...π(fluorenyl) interactions are observed. Basic synthons, in combination with the Long-Range Synthon Aufbau Modules, further supported by energy-framework calculations, are discussed. Furthermore, the relevance of Fmoc-based supramolecular hydrogen-bonding patterns in biocomplexes are emphasized, for the first time.

The success of innovative drugs depends on an interdisciplinary and holistic approach to their design and development. The supramolecular architecture of living systems is controlled by non-covalent interactions to a very large extent. The latter are prone to extensive cooperation and like a virtuoso play a symphony of life . Thus, the design of effective ligands should be based on thorough knowledge on the interactions at either a molecular or high topological level. In this work, we emphasize the importance of supramolecular structure and ligand-based design keeping the potential of supramolecular H-bonding synthons in focus. In this respect, the relevance of supramolecular chemistry for advanced therapies is appreciated and undisputable. It has developed tools, such as Hirshfeld surface analysis, using a huge data on supramolecular interactions in over one million structures which are deposited in the Cambridge Structure Database (CSD). In particular, molecular interaction surfaces are useful for identification of macromolecular active sites followed by in silico docking experiments. Ornithine-derived compounds are a new, promising class of multi-targeting ligands for innovative therapeutics and cosmeceuticals. In this work, we present the synthesis together with the molecular and supramolecular structure of a novel ornithine derivative, namely N -α, N -δ)-dibenzoyl-(α)-hydroxymethylornithine, 1 . It was investigated by modern experimental and in silico methods in detail. The incorporation of an aromatic system into the ornithine core induces stacking interactions, which are vital in biological processes. In particular, rare C=O … π intercontacts have been identified in 1 . Supramolecular interactions were analyzed in all structures of ornithine derivatives deposited in the CSD. The influence of substituent was assessed by the Hirshfeld surface analysis. It revealed that the crystal packing is stabilized mainly by H … O, O … H, C … H, Cl (Br, F) … H and O … O interactions. Additionally, π … π, C-H … π and N-O … π interactions were also observed. All relevant H-bond energies were calculated using the Lippincott and Schroeder H-bond model. A library of synthons is provided. In addition, the large synthons ( Long-Range Synthon Aufbau Module ) were considered. The DFT optimization either in vacuo or in solutio yields very similar molecular species. The major difference with the relevant crystal structure was related to the conformation of terminal benzoyl C15-C20 ring. Furthermore, in silico prediction of the extensive physicochemical ADME profile (absorption, distribution, metabolism and excretion) related to the drug-likeness and medicinal chemistry friendliness revealed that a novel ornithine derivative 1 has the potential to be a new drug candidate. It has shown good in silico absorption and very low toxicity., Competing Interests: The authors declare no conflict of interest.

Farmland soil typical for the Polish rural environment was used in pot experiment to estimate the impact of cadmium and zinc on the manganese, lead and copper uptake by lemon balm (Melissa officinalis L). Bioavailable and total forms of investigated metals in soil and metal concentrations in plants were determined by atomic absorption spectrometry. The plant photosynthesis indicators were also examined. Intensification of photosynthesis upon the high zinc and cadmium soil supplementation was observed. This effect was not detected at low metal concentrations. ANOVA proved that cadmium and zinc treatments influenced manganese, lead and copper transfer from soil and their concentration in plants. Zinc uptake and accumulation in either roots or above-ground parts in plant was inversely proportional to cadmium concentration in soil. Manganese concentration in roots decreased upon the soil supplementation with either zinc or cadmium. It suggests that the latter ions are transported via symplastic pathways and compete with manganese for similar transporters. The opposite situation was observed for lead and copper. Soil supplementation with cadmium and zinc affects manganese, lead and copper concentrations and photosynthesis intensity in lemon balm plant. The following combined interactions in either normal or stress conditions are important indicators of the migration pathways.

The crystal structure of the new polymorphic form of 3-aminoflavone (3-AF) has been determined by single crystal X-ray diffraction. This report presents results of fluorimetric studies on 3-AF in methanol and aquatic solvents. Based on 3D fluorescence emission spectra, optimal values for excitation (λ ex ) and emission/analytical (λ em ) wavelength, the analytical concentration range as well as the range of concentration quenching for the studied compound were established. Moreover, the limit of detection (LOD) and the limit of quantification (LOQ) were determined. The results were compared with those obtained using the standard UV-Vis absorption spectrophotometric method. The effect of acidity (pH) and the concentration of halide anions (chlorides, bromides, iodides and fluorides) on fluorescence quenching were analysed.

Lemon balm ( Melissa officinalis ) is a popular herb widely used in medicine. It is often cultivated in soils with substantial heavy metal content. Here we investigate the associated effects of cadmium and copper on the plant growth parameters augmented by the manganese, zinc, and lead uptake indicators. The concentration of all elements in soil and plants was determined by the HR-CS FAAS with the ContrAA 300 Analytik Jena spectrometer. Bioavailable and total forms calculated for all examined metals were augmented by the soil analyses. The index of chlorophyll content in leaves, the activity of net photosynthesis, stomatal conductance, transpiration rate, and intercellular concentration of CO 2 were also investigated. Either Cd or Cu acting alone at high concentrations in soil are toxic to plants as indicated by chlorophyll indices and gas exchange parameters. Surprisingly, this effect was not observed when both metals were administered together. The sole cadmium or copper supplementations hampered the plant's growth, lowered the leaf area, and altered the plant's stem elongation. Analysis of variance showed that cadmium and copper treatments of lemon balm significantly influenced manganese, lead, and zinc concentration in roots and above ground parts.

Polycystic ovary syndrome (PCOS) is the most common reproductive endocrine disorder in females with insulin resistance playing a key role in pathogenesis. The objective of this study was to investigate current trends and future implications of multidisciplinary PCOS clinics with inclusion of dietitians. A two-phase, formative investigation on practitioners was conducted through an anonymous survey followed by focus groups. Survey respondents included 261 health care providers from around the world; the majority (59%) representing multidisciplinary teams. Focus group participants included four dietitians, three physicians, a health psychologist and a licensed nutritionist. Primary barriers for future multidisciplinary clinics included: money/resources, insurance reimbursement, and difference of opinions. Potential advantages included: more comprehensive and integrated care, greater convenience/efficiency, and better long-term outcomes. A majority of respondents (89%) stated that dietitians should be 'involved' or 'highly involved' in treatment. The greatest challenges for dietitians include insurance, limited disease knowledge, and lack of referrals. Most providers agreed that multidisciplinary clinics would lead to a better prognosis. A greater emphasis needs to be placed on educating professionals on the importance of nutrition counseling. Access to educated dietitians is likely the best way to ensure that PCOS patients have access to lifestyle interventions.

Polycystic ovarian syndrome (PCOS) is thought to be the most common endocrine disorder found in women. Common symptoms include irregular menstrual cycle, polycystic ovaries, and hirsutism, as well as an increased risk for a multitude of conditions, including insulin resistance, dyslipidemia and infertility. The prevalence of polycystic ovarian syndrome is generally thought to be between 3% and 10% but it is widely unknown for specific subpopulations based on geographical location and race/ethnicity. Based on the high degree of variability and inconsistencies between the different diagnostic criteria, there is a unique challenge that exists when determining the prevalence of this syndrome. There are a large percentage of individuals that remain undiagnosed even after visiting multiple health care providers. Most studies conducted across the world are limited by small sample size, selection bias, and lack of comparability across studies. There have been very few studies that have examined the prevalence of polycystic ovary syndrome across the United States. Based on the National Institutes of Health (NIH)'s diagnostic criteria, there is a similar prevalence of PCOS documented across the United States, the United Kingdom, Spain, Greece, Australia, and Mexico. Other studies have shown some differences between geographical location and race. The existing data is not conclusive enough to determine whether or not there is any significant differences in the prevalence of PCOS across geographical location, racial or ethnic groups. This review will seek to determine the prevalence of polycystic ovarian syndrome based on geographical location and race/ethnicity.

Polycystic Ovarian Syndrome (PCOS), with common symptoms of irregular menstrual cycles, ovarian cysts, and hirsutism, is thought to be the most common endocrine disorder found in women, and use of multidisciplinary teams has been shown to be effective. The purpose of this review is to determine the future need for specialized, comprehensive, multidisciplinary treatment for PCOS and the current description and efficacy of existing multidisciplinary clinics. The literature was searched using PubMed, CINAHL, PsycINFO, Medline, and the Cochrane Library. Keywords included treatment efficacy, polycystic ovary syndrome, treatment and collaboration. Results showed that while an increasing number of studies continue to come out expressing the need for multidisciplinary approaches to and clinics for the treatment of PCOS, there is still a large gap in the literature documenting actual multidisciplinary PCOS treatment facilities. The limited literature documenting the efficacy of multidisciplinary PCOS clinic have demonstrated increased weight loss, high patient satisfaction, and high retention compared to single-care providers. Data showed that these teams are most commonly made up of a combination of endocrinologists, psychologists, dietitians, gynecologists, and endocrine-specialized nurses. Data showed that there is a high degree of variability and rates of diagnosis between types of single-care providers, such as: endocrinology, dermatology, gynecology, and fertility. Individuals with PCOS are in need for specialized, individualized, and focused care from a diverse team of healthcare providers to treat PCOS comprehensively., Competing Interests: The authors declare no conflict of interest.

An efficient synthetic strategy to 3-methylidene-2,3-dihydroquinolin-4(1H)-ones variously substituted in position 2 has been developed. The title compounds were synthesized in the reaction sequence involving reaction of diethyl methylphosphonate with methyl 2-(tosylamino)benzoate, condensation of thus formed diethyl 2-oxo-2-(2-N-tosylphenyl)ethylphosphonate with various aldehydes followed by successful application of the obtained 3-(diethoxyphosphoryl)-1,2-dihydroquinolin-4-ols as Horner-Wadsworth-Emmons reagents for the olefination of formaldehyde. Also, enantioselective approach to the target compounds has been evaluated using 3-dimenthoxyphosphoryl group as a chiral auxiliary. Single X-ray crystal analysis of (2S)-3-(dimenthoxyphosphoryl)-2-phenyl-1-tosyldihydroquinolin-4-ol revealed the presence of strong resonance-assisted hydrogen bond (RAHB). The obtained 3-methylidene-2,3-dihydroquinolin-4(1H)-ones were then tested for their cytotoxic activity against two leukemia cell lines NALM-6 and HL-60 and a breast cancer MCF-7 cell line. All compounds showed very high cytotoxic activity with the IC 50 values mostly below 1 μm in all three cancer cell lines. The selected analogs were also tested on human umbilical vein endothelial cells (HUVEC) and on human mammary gland/breast cells (MCF-10A) to evaluate their influence on normal cells. Since one of the most serious problems in cancer chemotherapy is the development of drug resistance, the mRNA levels and activity of ABCB1 transporter considered to be the most important factor engaged in drug resistance, were evaluated in MCF-7 cells treated with two selected analogs. Both compounds were strong ABCB1 transporter inhibitors that could prevent efflux of anticancer drugs from cancer cells., (© 2018 Wiley-VHCA AG, Zurich, Switzerland.)

The novel crystal structures of ethyl (S)-P-(4-oxo-4H-benzo[4,5]thiazolo[3,2-a]pyrimidin-3-yl)-N-[(R)-1-phenylethyl]phosphonamidate, C 20 H 20 N 3 O 3 PS, I, and diethyl (4-isopropyl-2-oxo-3,4-dihydro-2H-benzo[4,5]thiazolo[3,2-a]pyrimidin-3-yl)phosphonate, C 18 H 25 N 2 O 4 PS, II, were characterized by X-ray diffraction analysis. The crystal packing of I is dominated by two infinite stacks composed of symmetry-independent molecules linked by distinctively different hydrogen-bond systems. The structure of II shows a ladder packing topology similar to those observed in related phosphorylated azaheterocycles. Structural studies are supplemented by calculations on the interactions stabilizing the molecular assemblies using the PIXEL method. Additionally, fingerprint plots derived from the Hirshfeld surfaces were generated for each structure to characterize the crystal packing arrangements in detail. The aromaticities of the heterocyclic moieties have been investigated using HOMA and HOMHED parametrization and compared with structures reported previously.

N6-Threonylcarbamoyladenosine (t6A) and its derivatives are universally conserved modified nucleosides found at position 37, 3΄ adjacent to the anticodon in tRNAs responsible for ANN codons. These modifications have pleiotropic functions of tRNAs in decoding and protein synthesis. In certain species of bacteria, fungi, plants and protists, t6A is further modified to the cyclic t6A (ct6A) via dehydration catalyzed by TcdA. This additional modification is involved in efficient decoding of tRNALys. Previous work indicated that the chemical structure of ct6A is a cyclic active ester with an oxazolone ring. In this study, we solved the crystal structure of chemically synthesized ct6A nucleoside. Unexpectedly, we found that the ct6A adopted a hydantoin isoform rather than an oxazolone isoform, and further showed that the hydantoin isoform of ct6A was actually present in Escherichia coli tRNAs. In addition, we observed that hydantoin ct6A is susceptible to epimerization under mild alkaline conditions, warning us to avoid conventional deacylation of tRNAs. A hallmark structural feature of this isoform is the twisted arrangement of the hydantoin and adenine rings. Functional roles of ct6A37 in tRNAs should be reconsidered., (© The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: Impact of two widely used commercial herbicides, i.e. Aminopielik D 450 SL and Chwastox 300 SL, on the uptake and translocation of selected heavy metals in wheat plants Triticum aestivum L. cultivated in the laboratory pot experiments was investigated. Mineral-humus, loamy sand soil representative for the central part of Poland was applied. Bioavailable, exchangeable and total forms of Cd, Co, Cu, Zn, Pb, and Mn were determined. Transfer coefficients, translocation, and bioaccumulation factors illustrating metal migration in the plant were investigated., Results: Administration of commercial herbicides significantly altered heavy metals uptake by wheat in a way distinctively different than that observed for the parent chemically pure synthetic auxins, i.e. 2,4-D and MCPA. In particular, Aminopielik D 450 SL and Chwastox 300 SL prompted heavy metals accumulation in roots as indicated by their high transfer coefficients. Further transport to above ground part of the plant was limited and element dependent., Conclusions: This work clearly shows that commercial herbicide formulations may act in a distinctively different way than pure active ingredients alone.

Mineralization to the complete oxidation of sample carbon component does not always assure the best analyte recovery. Particular attention should be paid to the presence of silicon in the investigated plant sample and especially in the certified reference material for which Si content is scarcely given by the providers. During mineralization without addition of the hydrofluoric acid, the residual carbon may block silica surfaces and increase availability of an analyte for its spectral determination in the solution. This issue is of particular relevance because standard protocols for digestion of plant matrices often do not support hydrofluoric acid addition. Several procedures recommended for decomposition of herbal plants were applied for the respective certified reference material and examined in detail. Manganese, copper, and zinc contents were analyzed in all samples by the flame atomic absorption spectrometry. Additionally, the residual carbon was determined in all mineralizates. Silicon content was analyzed by the X-ray fluorescence method. The best recoveries were observed for samples characterized by relatively high residual carbon.

The aim of the study was to estimate the influence of the 2,4-dichlorophenoxy acetic acid and 2-methyl-4-chlorophenoxyacetic acid on the uptake and translocation of Cd, Co, Ni, Cu, Zn, Pb and Mn by wheat (Triticum aestivum L.). Two farmland soils typical for the central Polish rural environment were used. Studies involved soil analyses, contents of bioavailable, exchangeable and total forms for all investigated metals. Atomic absorption spectrometry was used to determine the concentration of the elements. The best correlation between the herbicide rate and the metal concentration was visibly for the underground part of plants. Analysis of variance proved that herbicide treatment of wheat frequently influences the metal transfer from soil and their concentration in roots and shoots. In particular, higher herbicide rates prompted the significant increase of all metals concentration in roots. Additionally, transfer coefficients depended on the type of soil and the herbicide rate applied. Uptake of metals may be also influenced by the formation of sparingly water-soluble metal-herbicide complexes. Its intensity would then depend on the solubility of particular chemical entity with the low solvable Pb, Cu and Cd complexes being the least mobile., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Basil ( Ocimum basilicum L.) is extensively cultivated as either an important spice and food additive or a source of essential oil crucial for the production of natural phenylpropanoids and terpenoids. It is frequently attacked by fungal diseases. The aim of the study was to estimate the impact of thiuram contact time on the uptake of manganese, cobalt, nickel, copper, zinc, cadmium, and lead by Ocimum basilicum L . The relevant plant physiological parameters were also investigated. Two farmland soils typical for the Polish rural environment were used. Studies involved soil analyses, bioavailable, and total forms for all investigated metals, chlorophyll content, and gas exchange. Atomic absorption spectrometry was used to determine concentration of all elements. Analysis of variance proved hypothesis that thiuram treatment of basil significantly influences metal transfer from soil and their concentration in roots and aboveground parts. This effect is mostly visible on the 14th day after the fungicide administration. Thiuram modifies mycoflora in the rhizosphere zone and subsequently affects either metal uptake from the soil environment or their further migration within the basil plant. Notable, those changes are more evident for basil planted in mineral soil as compared to organic soil with higher buffering capacity.

The aim of the study was to estimate the influence of soil pH on the uptake of copper, zinc, and manganese by Valeriana officinalis . Preliminary studies involved soil analyses to determine acidity, organic matter content, and copper, zinc, and manganese total and bioavailable forms. The study involved atomic absorption spectrometry to determine the concentration of the elements, and mineral soil of pH = 5.1 was used in the study, as being typical for central Poland. The copper, zinc, and manganese contents were determined in plants grown in soils which had been modified to cover a wide range of pH values 3÷13. The intensity of germination was strongly pH dependent with the highest yield obtained in original, unmodified soil. Surprisingly, high soil alkalinity stimulated copper and manganese uptake while at the same time resulting in a decrease in zinc content.

Two silver(I) complexes--[Ag(4-pmOpe)]NO₃}(n) and [Ag(2-bimOpe)₂]NO₃--and three copper(II) complexes--[Cu₄Cl₆O(2-bimOpe)₄], [CuCl₂(4-pmOpe)₂], and [CuCl₂(2-bis(pm)Ope]--were synthesized by reaction of silver(I) nitrate or copper(II) chloride with phosphate derivatives of pyridine and benzimidazole, namely diethyl (pyridin-4-ylmethyl)phosphate (4-pmOpe), 1H-benzimidazol-2-ylmethyl diethyl phosphate (2-bimOpe), and ethyl bis(pyridin-2-ylmethyl)phosphate (2-bis(pm)Ope). These compounds were characterized by ¹H, ¹³C, and ³¹P NMR as well as IR spectroscopy, elemental analysis, and ESIMS spectrometry. Additionally, molecular and crystal structures of {[Ag(4-pmOpe)]NO₃}n and [Cu₄Cl₆O(2-bimOpe)₄] were determined by single-crystal X-ray diffraction analysis. The antimicrobial profiles of synthesized complexes and free ligands against test organisms from the ATCC and clinical sources were determined. Silver(I) complexes showed good antimicrobial activities against Candida albicans strains (MIC values of ∼19 μM). [Ag(2-bimOpe)₂]NO₃ was particularly active against Pseudomonas aeruginosa and methicillin-resistant Staphylococcus epidermidis, with MIC values of ∼5 and ∼10 μM, respectively. Neither copper(II) complexes nor the free ligands inhibited the growth of test organisms at concentrations below 500 μg mL⁻¹., (Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

This paper presents the synthesis and solution conformational studies of the tripeptides Fmoc-Ala-(R)-(αMe)Ser(Ψ(H,H)Pro)-Ala-OBu(t) (6a) and Fmoc-Ala-(S)-(αMe)Ser(Ψ(H,H)Pro)-Ala-OBu(t) (6b). Additionally, the X-ray structure of 6a is given. NMR analysis corroborated by theoretical calculations (XPLOR) shows that in both peptides the amide bond between pseudoproline and the preceding amino acid is in the trans conformation. The same amide bond geometry was observed in the crystal state of 6a. The latter is additionally influenced by the presence of two symmetrically independent molecules in an asymmetric unit. Both molecules adopt a conformation which resembles β-turn type II, stabilized by hydrogen bonding. The conformational preferences and prolyl cis-trans isomerization of Ac-(αMe)Ser(Ψ(H,H)Pro)-NHMe (7) were explored at the IEFPCM/B3LYP/6-31+G(d) level of theory in vacuum, water and chloroform. It has been shown that the trans isomer predominates in water solutions and the cis isomer is preferred in chloroform. The conformation of 7 is down-puckered independently of the geometry of the amide bonds, with lower puckering in the transition state of the cis-trans isomerization.

In the crystal structure of the title compound, C(5)H(8)N(2)O(3), the mol-ecules exist in the zwitterionic form. The pyrrolidine ring adopts an envelope conformation with the unsubstituted endocyclic C atom situated at the flap. The other four endocyclic atoms are coplanar with the exocyclic carbonyl O atom, with an r.m.s. deviation from the mean plane of 0.06 Å. The carboxyl-ate substituent is located axially, while the ammonium group occupies an equatorial position. In the crystal structure, the mol-ecules are linked through N-H⋯O hydrogen bonds, forming a three-dimensional network.

Background: Diabetes is a powerful predictor of adverse events in patients undergoing percutaneous coronary intervention. Drug-eluting stents reduce restenosis rates compared with bare metal stents; however, controversy remains regarding which drug-eluting stents provides greater benefit in patients with diabetes. Accordingly, we compared the safety and efficacy of sirolimus-eluting stents (SES) with paclitaxel-eluting stents (PES) among diabetic patients in a contemporary registry., Methods and Results: Using the National Heart, Lung, and Blood Institute Dynamic Registry, we evaluated 2-year outcomes of diabetic patients undergoing percutaneous coronary interventions with SES (n=677) and PES (n=328). Clinical and demographic characteristics, including age, body mass index, insulin use, left ventricular function, and aspirin/clopidogrel use postprocedure, did not differ significantly between the groups except that PES-treated patients had a greater frequency of hypertension and hyperlipidemia. At the 2-year follow-up, no significant differences were observed between PES and SES with regard to safety or efficacy end points. PES- and SES-treated patients had similar rates of death (10.7% versus 8.2%, P=0.20), death and myocardial infarction (14.9% versus 13.6%, P=0.55), repeat revascularization (14.8% versus 17.8%, P=0.36), and stent thrombosis (1.3% versus 1.3%, P=0.95). After adjustment, no significant differences between the 2 stent types in any outcome were observed., Conclusions: PES and SES are equally efficacious and have similar safety profiles in diabetic patients undergoing percutaneous coronary interventions in clinical practice.